Materials must meet demanding criteria in order to function effectively in a biocompatible role, where sustained intimate contact with the internal or external tissues of a living organism is required. Contact lenses for ophthalmic applications must meet particularly demanding criteria, and materials from which lenses are made must therefore also possess a demanding combination of properties. A lens material must be sufficiently oxygen permeable to allow adequate oxygen to permeate through it so as to sustain the corneal health of the wearer. Lenses must be sufficiently physically robust to retain their integrity while being worn in the wearer's eye, as well as during handling, insertion, and removal. During wear, lens surfaces must be wettable and lubricious, while concomitantly resisting deposition of proteins, lipids, and other biochemical compounds. Lens material must also be highly transparent, and lenses that are soft and highly pliable are generally more comfortable to wear.
Some of the above characteristics are difficult to achieve concomitantly. Rigid ophthalmic lenses have good visual clarity and are generally sufficiently physically robust, but their lack of pliability, among other factors, can make them uncomfortable for some users to wear. Soft contact lenses have a lower tensile modulus that makes them more comfortable to wear, but decreased modulus often comes at the expense of decreased tear strength. Moreover, soft ophthalmic lenses typically cover a larger area and conform closely to the contour of the surface of an eye than rigid ophthalmic lenses. Accordingly, soft ophthalmic lenses typically need to have sufficient oxygen permeability to avoid corneal hypoxia.
Ophthalmic lenses made of non-silicone hydrogels typically have moderate to high water content (38-75%) and, provided the lens is sufficiently thin, can be fabricated to exhibit viable oxygen permeability with a satisfactory level of wettability. However, elevated oxygen permeability characteristics are difficult to attain with non-silicone hydrogels, and high water content hydrogels can be physically unstable, having a tendency to reduce in size with increases in temperature. In addition, thin lenses made from materials with high water content are also prone to dehydrate on the eye, which can result in lower on-eye oxygen permeability and which can in some instances lead to serious clinical complications. For lathe cut lenses, which often have increased thickness compared to cast-molded lenses, oxygen transmissibility levels can approach undesirably low values.
Silicone hydrogels generally have higher oxygen permeability than non-silicone hydrogels, but high silicone content can result in increased modulus and low surface energy properties that lead to poor wettability and to deposition of biological materials, especially lipids, on lens surfaces. High silicone content material also tends to be difficult or impossible to lathe at or above room temperature, thereby making manufacture of ophthalmic lenses by lathing silicone hydrogel material impractical. Silicone hydrogel material that has a Tg at or near room temperature may nonetheless be difficult or impossible to lathe at room temperature because cutting the silicone hydrogel with a lathe leads to the warming of the material being cut. Lowering silicone content typically results in decreased oxygen permeability where equilibrium water content remains constant.
Ophthalmic lenses made from silicone hydrogels can achieve an adequate, albeit not optimal, balance of surface wettability and resistance to deposition, modulus of elasticity, tear resistance, and oxygen permeability. However, manufacturing silicone hydrogel polymers and lenses therefrom introduces problems that are difficult and/or expensive to overcome. Moreover, it can be difficult to simultaneously achieve high oxygen permeability, low modulus and a viable level of wettability in silicone hydrogels, and conversely it can be difficult to attain high water content silicone hydrogels that possess sufficient silicone content to exhibit desirable oxygen permeability characteristics. An additional complication is that lenses comprising high water content silicone hydrogels including abundant N,N-dimethyl acrylamide and N-vinyl pyrrolidone tend to swell incrementally when stored in water or aqueous buffer for extended periods, limiting the shelf life of such lenses. Finally, silicone hydrogel lenses that have high water content tend to suffer from high water loss rates that result in undesirable dehydration of both lenses and wearers' eyes.
Silicon-containing monomers and hydrophilic monomers, from which silicone hydrogels are typically formulated, tend to resist amalgamation and instead form separate phases in polymerization reaction mixtures comprising relatively high concentrations of the hydrophilic and silicon-containing monomers. Manufacture of silicone hydrogels is thus complicated by the tendency of polymerization reaction mixtures to segregate into predominantly hydrophilic and hydrophobic phases, which can negatively impact both the course of the polymerization and the silicone hydrogel polymer thus formed. Silicon-containing monomers are often chemically modified to form prepolymers or macromonomers with relatively hydrophilic substituents that can be used in higher proportions than monomers containing exclusively silicone functionalities. Such silicon-containing prepolymers and macromonomers can be mixed more readily with hydrophilic monomers, helping to avoid phase segregation in polymerization reaction mixtures comprising relatively high concentrations of these silicon-containing species.
U.S. Pat. No. 4,711,943 (the Harvey patent) discloses silicone hydrogels comprising modified silicon-containing monomers, the modified silicon-containing monomers comprising a urethane linkage. Harvey discloses silicone hydrogels having exceptional putative physical properties. One example of silicone hydrogels disclosed in Harvey purportedly has a fully hydrated water content of 50.3%, oxygen permeability of 43 Barrers, and an exceptionally low modulus of elasticity of 1.6×10−6 dynes/cm2 (1.6×10−13 MPa; see Sample A, Harvey Table XII). However, this modulus value is not credible. Persons of ordinary skill in the art recognize that 1.6×10−6 dynes/cm2 is an unfeasibly low modulus value, approximately 12 to 14 orders of magnitude below a sensible number. Accordingly, it is tempting to suggest that the author(s) of the Harvey patent were confused about the sign on the exponent, and the modulus value should be a more reasonable 1.6×106 dynes/cm2. However, 1.6×106 dynes/cm2 (0.16 MPa) remains a very low modulus value for a silicone hydrogel, especially one comprising 43.38% N-[tris(trimethylsiloxy)silylpropyl]methacrylamide (TSMAA), leading persons of ordinary skill to reasonably surmise that the absolute value of the modulus exponent is incorrect as well as the sign.
Further evidence that modulus values disclosed in the Harvey patent are unfounded is shown in many other tables, and particularly in Table XIX, where modulus values of about 1.9×10−10 dynes/cm2 (1.9×10−17 MPa) are disclosed in silicone compositions containing 35% to 40% TSMAA. Such values are inconceivably low.
In summary, the Harvey patent discloses modulus values that defy credibility by persons of ordinary skill in the art. Accordingly, modulus figures disclosed in Harvey are not convincing. Nevertheless, Harvey discloses a silicone hydrogel embodiment with fully hydrated water content of 58.2% and oxygen permeability (Dk) of 35.2 Barrers, and another silicone hydrogel embodiment with oxygen permeability (Dk) of 58 Barrers and water content of 37.6%. These water content and oxygen permeability values are fully plausible in that the Dk values are elevated above what would be predicted exclusively on the basis of the equilibrium water contents (EWC) of these polymers using the Benjamin and Young ‘Dk-EWC’ correlation [log(Dk)=0.01754 (% GEWC)+0.3897],1 where % GEWC is the gravimetric EWC, for which a conventional 35.2% (EWC) polymer would be predicted to exhibit a Dk of 10.2 Barrers and a 37.6% (EWC) polymer a Dk of 11.2 Barrers. 1 Young, Matthew D.; Benjamin, William J., Eye & Contact Lens: Science & Clinical Practice: April 2003-Volume 29-Issue 2-pp 126-133.
U.S. Pat. No. 5,486,579 (the Lai patent) discloses silicone hydrogel compositions comprising silicon-containing monomers with urethane linkages. The silicone hydrogels disclosed in Lai have varied water content and modulus of elasticity that are adjusted by varying abundance of hydrophilic monomers, including N-vinyl pyrrolidone (NVP) and N,N-dimethyl acrylamide (DMA). Lai discloses silicone hydrogels with modulus values as low as 0.62 MPa (6.2×106 dynes/cm2) at 37% fully hydrated water content (Table 1), but does not disclose any fully hydrated water content above about 46% (Table 1), and no modulus below 0.62 MPa.
Interestingly, the Lai patent claims modulus values as low as 0.05 MPa (5.0×105 dynes/cm2 in claims 5 and 15), an exceptionally low but not inconceivable value. However, Lai does not disclose how a person of ordinary skill in the art might achieve such low modulus in silicone hydrogels. Moreover, it is not implicit that silicone hydrogel formulations such as those disclosed in Lai could achieve modulus values lower than those of the specific examples disclosed.
Conversely, the Lai patent suggests that silicone hydrogels preferably have oxygen permeability of Dk>60 Barrers (Lai column 6, lines 58-59). A person of ordinary skill in the art would recognize that Dk>60 Barrers is possibly an inherent quality in a silicone hydrogel composition such as disclosed in Lai, examples of which contain about 30%-47% TRIS (Lai columns 9 and 10) and an equilibrium water content≦46%. Lai does not, however, explicitly enable a person of ordinary skill in the art to make a silicone hydrogel with oxygen permeability>60 Barrers.
In summary, the Lai patent discloses silicone hydrogels with fully hydrated water content around 25% to 46% that also have modulus values of 0.62 MPa to 0.85 MPa (6.3×106 dynes/cm2 to 8.5×106 dynes/cm2). Lai does not disclose how a person of ordinary skill in the art can make a silicone hydrogel with a modulus below 0.62 MPa, and embodiments of hydrogels and processes for making hydrogels exemplified in Lai do not implicitly achieve the low modulus claimed in Lai claims 5 and 15.
U.S. Pat. No. 6,649,722 (the Rosenzweig patent) discloses silicone hydrogel compositions that achieve relatively high oxygen permeability (Dk=117 Barrers) at moderately low water content (32%), and lower oxygen permeability (88 Barrers) at higher water content (46%). Rosenzweig discloses silicone hydrogels with water content as high as 53%, but does not disclose a Dk value for 53% water content silicone hydrogel. The Rosenzweig disclosure shows a loose inverse correlation between water content and oxygen permeability in the Rosenzweig silicone hydrogels. Rosenzweig also discloses numerous silicone hydrogels that comprise styrene or substituted styrene.
United States Patent Application No. 2006/0004165 (the Phelan application) discloses silicone hydrogel compositions that are prepared from reaction mixtures comprising urethane macromonomers and styrene or substituted styrene monomers. Examples of silicone hydrogel material disclosed in Phelan have oxygen permeability≧65 Barrers and glass transition temperatures (Tg) in a 60-68° C. range. Interestingly, Phelan discloses room temperature lathability and associated property Tg of 60° to 68° in silicone hydrogels comprising styrene or substituted styrenes that are remarkably similar to silicone hydrogels comprising styrene or substituted styrene disclosed in Rosenzweig.